The object of this research is to understand the biochemistry and molecular biology involved in the replication of chromosomes in mammalian cells. This includes the processes of initiation, elongation aad termination of DNA synthesis, as well as the structure of chromatin and the mechanism of its disassembly and reassembly. I anticipate that this work will lead directly to a better understanding of mammalian cell proliferation. As a simple but well defined model of mammalian chromosomes, we are studying the replication of the small DNA tumor virus, Simian virus 40. In vitro systems have been developed that permit the continuation of both viral DNA replication and chromosome assembly. These systems have been used to investigate the molecular mechanisms and enzymology of DNA synthesis at normal replication forks, the structure of the nucleoprotein complex before, at and after the replication forks, and the overall progress and control of replication in a single replicon.